Studies during the past year have focused on the further characterization of both the adenosine receptor and the adenosine uptake site in brain, with particular focus on the uptake site. We have tritiated a new ligand (3H dipyridamole (3H)DPR) for the uptake site and characterized it at both the membrane binding and autoradiographic levels, showing that it recognizes 3-4-fold more sites than does (3H) nitrobenzylthioenosine (3H)NBI. (3H)DPR has therefore enabled us to see much more of the total complement of adenosine uptake sites in brain than was previously possible. These data suggest that multiple populations of adenosine uptake sites may be present in brain. Adenosine uptake studies utilizing direct uptake of (3H) adenosine into synaptoneurosomes have been initiated, with the results showing that NBI inhibits uptake in a biphasic manner, again suggesting multiple uptake site subtypes. We have also shown by both binding and autoradiographic analysis that cerebellar adenosine receptors are increased in the Maudsley reactive strain of rats, suggesting that this rather specific biochemical parameter may account for some of the behavioral properties of these animals. Work has continued concerning the interrelationship between the adenosinergic system and the mechanisms of carbamazepine action, with results generated showing that this agent is probably an antagonist at adenosine receptors.